The present invention relates to a pharmaceutical product comprising a parasympathomimetic drug having therapeutic properties on the pathology of human sensitivity and of the motor system in general.
Parasympatnomimetic drugs are already known, the effect of which is similar to that which is obtained by stimulating the parasympathetic postganglionic fibres.
The fact is also known that these drugs are at present rarely used since their action throughout the sensory periphery is little known.
In this connection it should be pointed out that the Applicant has elaborated a theory about a "sympathetic-sensory coupling" (SSC), by postulating ubiquitous sympathetic inhibitions throughout the sensory periphery.
Considering the well-known sympathetic-parasympathetic parallelism on smooth muscle, glands and myocardium, the same Applicant has experimentally exploited the parasympathetic denervation supersensitivity of familial dysautonomia (Riley-Day disease)and he has reversed with parasympathomimetic drugs the skin and corneal analgesia, the ageusia, anosmia and proprioceptive and vestibular areflexia of this disease, thus experimentally showing for the first time the existence of excitatory "parasympathetic-sensory couplings" (PSC).
Moreover, he has integrated this discovery into the general theory of the "sympathetic and parasympathetic sensory coupling" (SPSC), and into the essential distinction between the following peripheries:
1) normechanoceptive, nornociceptive, norproprioceptive and PA1 2) dysmechanoceptive, dysnoeiceptive, dysproprioceptive.
This theory postulates the existence of normal normechanoceptors, nornociceptors and norproprioceptors which are excited by the parasympathetic system and inhibited by the sympathetic one; and that, in the case of a parasympathetic denervation, para. sympathetic drugs can replace the excitatory action of the parasympathetic system thereon.
Vice versa, in the case of a biochemical alteration of the axoplasmic flow of the primary sensory neurons, due to a central or peripheral cause, these neurons may display membrane dysmetabolic characteristics which transform normechanoceptors into dysmechanoceptors, nornociceptors into dysnociceptors, and norproprioceptors into dysproprioceptors.
On these dysmechanoceptors, dysnociceptors and dysproprioceptors, the parasympathetic nervous system reverses its action, from being excitatory on to the normechanoceptors, nornociceptors and norproprioceptors, into being an inhibitory one.
However, the parasympathetic action becomes very small or absent, because of the prevalence of an excitatory action of the sympathetic nervous system on dysmechanoceptors, dysnociceptors and dysproprioceptors.
The same Applicant has pointed out a broad applicability of this theoretical innovation particularly in the medical and neurological field.
Within this general heuristic context, the Applicant has exploited the denervation supersensitivity of parasympathetic denervation on sensory receptors, and he has elevated it to a conspicuous indication of the general principle of ubiquitous "parasympathetic-sensory couplings", which up to now have been almost unknown in the neurological field, because of the dogmatic and exclusive ideology of the unidirectionality of "sense" (from-periphery-to-center) and of motion (from-centre-to-periphery).
Substantially, by means of classical and modern aesthesiometric tests, such as the Stockholm thermotest (which measures the pain on the skin due to warm and cold), the "Zottmeter" (a new quick skin algometer) and by means of other aesthesiometric devices, such as that of Cochet-Bonnet and the "Leibnizmeter" for corneal aesthesia, the von Frey bristles for skin and mucous aesthesia, and the geusimeter for gustatory aesthesia, the Applicant has experimentally verified the above mentioned SPSC theory, in several clinical situations of hypoaesthesia and/or of cutaneous and corneal nornociceptive and normechanoceptive anaesthesia and of the oral mucosa.
In addition to more or less relatively rare neurological situations, but of great theoretical interest for veifying the SPSC theory, such as the above mentioned Riley-Day disease, ectodermal dysplasia, corneal hypoaesthesia due to acoustic neurinoma or to invasive pathology of the pontocerebellar angle, uremic neuropathy and leprosy, the same Applicant has moreover reversed, by means of parasympathomimetic drugs (in particular with carbachol and/or methacholine and/or ehtylether-beta methylcholine cloride and/or bethanechol, normechanoceptive and nornociceptive hypoaesthesias, in 315 out of 337 cases of diabetic neuropathy.
Moreover, the same Applicant has reversed, by means of the above mentioned drugs, skin normechanoceptive and nornociceptive hypoaesthesias and anaesthesias in 36 senile subjects both male and female (having an average age of 74.3 years), not affected by relevant pathologies. It was found that also their reaction times were improved.
The duration of the effect of a single dose was found to vary from 26 hours to 15 days depending on the cases.
That same effect, in particular, could be restored by means of a new administration.